AIM: Imatinib is a tyrosine kinase inhibitor that has revolutionized the treatment of chronic myeloid leukemia (CML). Despite its efficacy, about a third of patients discontinue the treatment due to therapy failure or intolerance. The rational identification of patients less likely to respond to imatinib would be of paramount clinical relevance. We have shown that transmembrane transporter hOCT1 genotyping predicts imatinib activity. In parallel, Polycomb group genes (PcGs) are epigenetic repressors implicated in CML progression and in therapy resistance...

The self-association of sterile alpha motifs (SAMs) into a helical polymer architecture is a critical functional component of many different and diverse array of proteins. For the Drosophila Polycomb group (PcG) protein Polyhomeotic (Ph), its SAM polymerization serves as the structural foundation to cluster multiple PcG complexes, helping to maintain a silenced chromatin state. Ph SAM shares 64% sequence identity with its human ortholog, PHC3 SAM, and both SAMs polymerize. However, in the context of their larger protein regions, PHC3 SAM forms longer polymers compared with Ph SAM...

Reaction conditions for the three-component synthesis of aryl 1,3-diketones are reported applying the palladium-catalyzed carbonylative α-arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)2] (dba=dibenzylideneacetone) as the palladium source and 1,3-bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two-chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO-releasing compound, 9-methylfluorene-9-carbonyl chloride (COgen)...

BACKGROUND: Polycomb group genes (PcGs) are epigenetic effectors implicated in most cancer hallmarks. The mutational status of all PcGs has never been systematically assessed in solid tumours. METHODS: We conducted a multi-step analysis on publically available databases and patient samples to identify somatic aberrations of PcGs. RESULTS: Data from more than 1000 cancer patients show for the first time that the PcG member PHC3 is amplified in three epithelial neoplasms (rate: 8-35%)...

Sterile alpha motifs (SAMs) are frequently found in eukaryotic genomes. An intriguing property of many SAMs is their ability to self-associate, forming an open-ended polymer structure whose formation has been shown to be essential for the function of the protein. What remains largely unresolved is how polymerization is controlled. Previously, we had determined that the stretch of unstructured residues N-terminal to the SAM of a Drosophila protein called polyhomeotic (Ph), a member of the polycomb group (PcG) of gene silencers, plays a key role in controlling Ph SAM polymerization...

In silico analyses have established that transcripts from some genes can be processed into RNAs with rearranged exon order relative to genomic structure (post-transcriptional exon shuffling, or PTES). Although known to contribute to transcriptome diversity in some species, to date the structure, distribution, abundance, and functional significance of human PTES transcripts remains largely unknown. Here, using high-throughput transcriptome sequencing, we identify 205 putative human PTES products from 176 genes...

Polyhomeotic homolog 3 (PHC 3) is a member of the human polycomb complex and has been regarded as a candidate tumor suppressor of osteosarcoma. In the present paper, we performed a mutation survey and PHC3 expression analysis by quantitative real-time PCR using 10 osteosarcoma cell lines and 42 primary osteosarcoma samples. Relative PHC3 expression values of clinical samples were analyzed with clinical outcomes, and it was suggested that lower PHC3-expressing patients had significantly worse overall survival...

1. The major effect associated with hydroxyurea (HU) treatment of sickle cell anaemia (SCA) patients is an increase in fetal haemoglobin (HbF) synthesis, which inhibits the polymerization of haemoglobin S. 2. Hydroxyurea improves clinical symptoms by reducing the frequency of pain and vaso-occlusive crises, acute chest syndrome, transfusion requirements and hospitalization. 3. The molecular mechanisms responsible for HU-mediated induction of fetal globin transcription are not completely understood. Therefore, the aim of the present study was to identify differentially expressed genes participating in these mechanisms...

Polyhomeotic-like 3 (PHC3) is a ubiquitously expressed member of the polycomb gene family and part of the human polycomb complex hPRC-H. We found that in normal cells PHC3 associated with both hPRC-H complex components and with the transcription factor E2F6. In differentiating and confluent cells, PHC3 and E2F6 showed nuclear colocalization in a punctate pattern that resembled the binding of polycomb bodies to heterochromatin. This punctate pattern was not seen in proliferating cells suggesting that PHC3 may be part of an E2F6-polycomb complex that has been shown to occupy and silence target promoters in G(0)...

The Polycomb group (PcG) gene products form multimeric protein complexes and contribute to anterior-posterior (A-P) specification via the transcriptional regulation of Hox cluster genes. The Drosophila polyhomeotic genes and their mammalian orthologues, Phc1, Phc2, and Phc3, encode nuclear proteins that are constituents of evolutionarily conserved protein complexes designated class II PcG complexes. In this study, we describe the generation and phenotypes of Phc2-deficient mice. We show posterior transformations of the axial skeleton and premature senescence of mouse embryonic fibroblasts associated with derepression of Hox cluster genes and Cdkn2a genes, respectively...

OBJECTIVE: To investigate whether all-trans retinoic acid (RA) has antitumor effect in vivo. METHODS: Sixteen nude mice were transplanted with human laryngeal cell carcinoma PHC3. Eight of them were injected with RA intraperitoneally and others with solvent as the control. Response was measured and tumor histopathological features were studied. RESULTS: The growth and weight of RA-treated tumors were significantly reduced in comparison with those of the control...

We have identified and characterised novel members of the mammalian polyhomeotic gene family, comprising a third human homologue, PHC3, and its mouse counterpart, Phc3. The two new genes have essentially the same genomic organisation, with 15 exons specifying proteins of 983 (PHC3) or 981 (Phc3) amino acids, with an overall sequence identity of 93%. Northern blot hybridisations have identified a single large transcript in a variety of adult mouse tissues and in situ hybridisation analyses indicate apparently ubiquitous expression during early human and mouse development...

In order to know whether laryngeal cancer draining lymph node lymphocytes (INL) have antitumor effects in vivo, we transfered IL-2 activated LNL to nude mice with human laryngeal squamous cell carcinoma line PHC3 xenografts, and observed a suppressive effect on tumor growth. It was also found in the epitype changes of LNL by indirect immunofluorencence method the major composition of freshly isolated LNL was CD3+ T cells in which there were more Th/i cells than Ts/c cells, CD4+/CD8+ ratio was 3.30 +/- 0.653...

The distribution of 3H-TdR labeled human laryngeal cancer drained lymph node lymphocytes (LNL) to human laryngeal squamous cell carcinoma were traced in PHC3 bearing nude mice, and the radioactivity in tissues was detected. 30.7% labeled cells were localized in live in first day after transfer, and a few in lung, spleen and kidney. Labeled cells were reduced weekly and by the end of the fourth week there were still 4.3% in live, but very few were detected in the tumor site. This indicated that cancer drained LNL had no specificity to tumor, and could not infiltrate into tumor sites...